Psychopharm Sleep

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Describe the role of the LC, Raphe, and TMN in awakefulness

They all directly stimulate wakefulness

Describe the role of the ORX in awakefulness

Act to promote the activity of monoamineric nuclei

Describe the role of VLPO and eVLPO in awakefulness

Inhibit sleep-promoting neurons in the VLPO, which in turn relieves inhibition of the monoaminergic cells and ORX neurons

Describe the role of ORX in sleep

The disinhibition of the VLPO neurons inhibits ORX neurons which in turn prevents activation of monoaminergic nuclei

Describe the role of LC, RN, and TMN in sleep

The VLPO neurons inhibit the monoaminergic neurons and in turn, relieve their own inhibition

Describe the role of VLPO in sleep

They directly promote sleep

Describe the mechanism of the "on and off switch" of the sleep center

Histamine from the TMN inhibits the VLPO to cause wakefulness and the GABA from the VLPO inhibits the TMN to cause sleep

Histamine 1 antagonists cause?

Sleepiness by binding to G-coupled protien messanger systems

Discuss the hyptonic and antidepressant doses for doxepin

Hyptonic dose = 1-6 mg and antidepressant dose = 300-1500 mg

What is the hypnotic and antidepressant doses of trazodone?

Hyptonic dose = 25-150 mg and antidepressant dose = 150-600 mg

What is the mechanism of caffeine?

It displaces adenosine which normally decreases the sensitivity of D2 receptors, thus causing increased dopaminergic actions

What Z drug has the shortest 1/2 life?

Zaleplon

What is the mechanism of Suvorexant (Belsomra) and Lemborexant (Dayvigo)?

Binding OX1R and OX2R causing G-coupled protein second messangers to lead to sleep

This drug is a dual-orexin receptor antagonist

Dayvigo

Because patients with depression have phase delayed sleep there is a lack of _____ production.

Melatonin

Alpha-1, M1, and H1 receptors are all associated with sedation. Name the neurotransmitters associated with them.

ACh, HA, and NE

It is believed that the increase in synaptic dopamine following blockade of DAT leads to increased tonic firing and downstream effects on neurotransmitters including those involved in wakefulness, such as histamine and orexin/hypocretin.

Modafinil

3 stages of consciousness

Awake, non-REM sleep, and REM sleep

Discuss the 4 stages of non-REM sleep

• Stage 1 – drowsy period, very light, theta activity • Stage 2 – Sleep spindles, bursts of activity d/t interactions between thalamus and cortex • Stages 3 & 4 – slow wave sleep, characterized by delta waves

Typical night how many episodes of non-REM/REM activity?

1st REM episode – after ____min of sleep

Name some conditions associated with REM latency

Exhaustion, depression, narcolepsy, and sleep apnea

• Limited eye movement • Decrease in muscle tone, muscles capable of movement but rarely do • Decrease in heart rate • Decrease in metabolic rate and body temperature • PET scan: decreased cerebral blood flow and energy metabolism

Non-REM sleep

• Rapid, darting movements of eyes • Paralysis of most major muscle groups, loss of skeletal muscle tone • Heart rate increases • Respiration rate increases • Penile/clitoral erections • PET scan: cerebral energy metabolism equal to that while awake

REM sleep

Non-REM sleep dreams

More like thoughts – like problem solving

REM sleep dreams

Illogical, bizarre, hallucinatory

Master clock of the brain

SCN

Mutations of _____ and ______ genes are found in delayed or advanced sleep phase syndromes

CLOCK and PER

What molecule is deficient in narcolepsy?

Orexin

Describe the sleep switch of the brain

SCN-Active during the day VLPO-Active during the night DMH-Intermediate step affecting eating, temperature, steroid cycle, sleep, and arousal

CSF moves from arteries through ____channels on BBB -> brain tissue -> out through veins taking molecular waste products

Glial

Spine formation increases while awake and decreases when we sleep

Pruning

Because nocturnal secretions of melatonin are prolonged in winter in patients with SAD, what can we do to help?

Early morning light therapy

How can we syncronize circadian rhythms and reduce manic episodes in patients with bipolar I?

Dark therapy and blue-blocking glasses

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